Homocysteine is a sulfur amino acid, and is an important intermediate for the metabolism of an essential amino acid, methionine. Homocysteine is maintained at an extremely low concentration in the cell, and redundant homocysteine is extracellularly released, i.e., into the blood. Thirty years ago, Dr. McCully reported that homocysteine causes vascular pathology such as arteriosclerosis and myocardial infarction (non-patent document 1). Thereafter, clinical tests verified that patients having arteriosclerosis in the peripheral vessel or cerebral vessel show high homocysteine values (non-patent document 2). In almost any clinical tests thereafter, a correlation between increased homocysteine value and cerebral infarction has been reported (non-patent documents 3-8). In a large scale test, it was reported that when the blood homocysteine value increases by 25% (3 μM in absolute value), the risk of coronary artery disease increases by 10%, and the risk of cerebral infarction increases by 20% (non-patent document 9), and it is now suggested that homocysteine is an independent risk factor.
At present, as a homocysteine-decreasing therapy, only an ingestion of a coenzyme of metabolic enzyme, i.e., vitamin B6, vitamin B12, folic acid, has been tried. Ingestion of these vitamins decreases the blood homocysteine value to some extent (non-patent document 10). Moreover, improvement in the vascular endothelial function and regression of carotid plaque by a vitamin therapy have been reported (non-patent documents 11-13).
However, in a large scale test aiming to examine an influence of vitamin therapy on the recurrence of cerebral infarction or myocardial infarction (The Vitamin Intervention for Stroke Prevention (VISP)), a recurrence preventive effect was not observed. The cause thereof is suggested to be the absence of a sufficient decrease in homocysteine by a vitamin therapy (non-patent document 14). This report has also clarified that the risk of recurrence of cerebral infarction can be decreased by 10% and the risk of myocardial infarction can be decreased by 26%, when the baseline of homocysteine value is lower by 3 μM. If the homocysteine value could be certainly decreased than the vitamin therapy, the onset of these events is expected to be suppressed significantly.
The enzyme that synthesizes homocysteine in the body is S-Adenosyl-L-homocysteine Hydrolase (hereinafter sometimes to be referred to as “SAHH”) alone. This enzyme controls a reaction to hydrolyze S-Adenosyl-L-homocysteine (hereinafter sometimes to be referred to as “SAH”) into Adenosine (hereinafter sometimes to be referred to as “Ado”) and Homocysteine (hereinafter sometimes to be referred to as “Hcy”) and a reversible reaction to conversely synthesize SAH from Adenosine and Homocysteine.
On the other hand, as a compound showing an SAHH inhibitory action, an adenine derivative (patent document 1) and a nitroprusside compound (patent document 2) have been reported. However, they have completely different structures from the structure of the present invention.
In addition, patent documents 3-7 report amide compounds. However, these reports do not disclose the present invention, and an SAHH inhibitory action is not reported (patent documents 3-7).